Abstract
Several studies have shown a tripartite link between food intake, seizures and cognitive deficits in epilepsy. Absence Epilepsy (AE) affect children during a critical phase of neurodevelopment. Limiting or even avoiding treatments based on antiepileptic drugs with strong side effects is extremely important. We investigated daily intermittent fasting (IF) as an innovative, drug-free method to improve seizure burden as well as cognitive deficits on different mouse models of AE. We implemented a 1-month daily IF regime (8 h feeding/16 h fasting) in control and epileptic mice followed by a multilevel analysis. We tracked the evolution of seizures (by electroencephalographic recordings) and behavioural comorbidities in the Grm7AAA KI mouse, an isomorphic model of "pure" AE. We show that the 1-month IF regime reduced significantly the occurrence of absence seizures by ~40%, while improving social and cognitive behavioural scores. RNA-seq experiments and preliminary gene ontology analysis revealed an altered mRNA expression pattern in the thalami of epileptic animals that was reversed by IF. In particular, modifications of angiogenesis-related genes were confirmed by blood vessels tracing experiments. Similar results were obtained in a pharmacological model of atypical absence seizures, the AY9944 mouse. Thus, our results indicate that daily IF could be a simple and efficient non-invasive strategy to be proposed as an alternative to the existing, yet often ineffective, anti-epileptic drugs or strict regimes, such as the ketogenic diet.